We are investigating the conformational tendencies of an imino-poor sequence within the alpha1(I) chain of type I collagen. The sequence GTPGPQGIAGQRGVV, referred to here as P15, shows a tendency to deviate from the triple-helical polyproline-II (ppII) conformation. Our previous studies suggest that this region has a tendency to adopt a conformation in which GIAG is in a beta-bend conformation, flanked by two regions in extended conformations. This is the most likely conformation adopted when bound to integrins. X-ray structures of inhibitors complexed with collagenase suggest that the GIAG region, which is the site of collagenase cleavage, is in an extended conformation when bound to this enzyme. The conformation of regions flanking the GIAG segment during binding to collagenase are unknown. We are thus examining the P15 region's conformational tendencies within collagen, in order to develop a model of how type I collagen interacts with collagenase. The conformational tendencies of collagen, as related to the collagen-collagenase complex, are relevant to the design of collagenase inhibitors for the prevention of tumor metastasis. We are performing molecular dynamics (MD) calculations on the P15 region within the collagen triple-helix. To enhance conformational sampling, we are also incorporating the multicanonical MD (MMD) algorithm into AMBER. Conformations derived from these simulations will be used in docking studies with collagenase. MidasPlus and the facilities of the UCSF Computer Graphics Laboratory have been used for graphical modeling and visualization of the molecular geometry, for preparing preparing starting structures for simulations, for monitoring the simulations.